The aims of this investigation are directed toward an understanding of the mechanisms and control of membrane-associated electron processes in M. phlei and the mode of action of the antitubercular drug isoniazid (INH) on such processes in mycobacteria. Studies will be performed to elucidate the role of water soluble complex S(G-25) containing MK-9(2H), phospholipid, and proteins and a lower molecular weight C fraction (which can be replaced by polyvalent anions) in restoring NADH oxidase activity to irradiated electron transport particles (ETP) in M. phlei. The NADH dehydrogenase will be purified, characterized, and the role of the above mentioned factors, as well as the effector NAD ion, will be studied to reconstitute and characterize the electron transport chain prior to cytochrome b. ETP depleted of phospholipids and MK-9(2H), and inactivated dehydrogenase will be used to characterize the insertion of these components into the natural membrane as well as in artifically prepared liposomes. The mode of action of INH will be studied in desensitizing the ETP to the effector INH. An INH resistant mutant which grows under anaerobic conditions will be characterized as to its metabolism and membrane-associated, energy-linked function. INH resistant strains isolated from patients will be used to determine whether these organisms can grow anaerobically. Similarily, an INH resistant mutant of C. fasciculata which can grow anaerobically will be characterized.